NM_000530.8(MPZ):c.418T>A (p.Ser140Thr) AND Charcot-Marie-Tooth disease type 1B

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Sep 23, 2025
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV006635477.1

Allele description [Variation Report for NM_000530.8(MPZ):c.418T>A (p.Ser140Thr)]

NM_000530.8(MPZ):c.418T>A (p.Ser140Thr)

Gene:

MPZ:myelin protein zero [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q23.3

Genomic location:

Preferred name:

NM_000530.8(MPZ):c.418T>A (p.Ser140Thr)

HGVS:

NC_000001.11:g.161306738A>T
NG_008055.1:g.8235T>A
NM_000530.8:c.418T>AMANE SELECT
NM_001315491.2:c.418T>A
NP_000521.2:p.Ser140Thr
NP_001302420.1:p.Ser140Thr
LRG_256t1:c.418T>A
LRG_256:g.8235T>A
NC_000001.10:g.161276528A>T
NM_000530.6:c.418T>A

Protein change:

S140T

Links:

dbSNP: rs572010627

Molecular consequence:

NM_000530.8:c.418T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001315491.2:c.418T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 1B
Synonyms:: CHARCOT-MARIE-TOOTH DISEASE, AUTOSOMAL DOMINANT, WITH FOCALLY FOLDED MYELIN SHEATHS, TYPE 1B; CHARCOT-MARIE-TOOTH DISEASE, SLOW NERVE CONDUCTION TYPE, LINKED TO DUFFY; CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 1B; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007307; MedGen: C0270912; Orphanet: 101082; OMIM: 118200

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV007520029	Variantyx, Inc.	criteria provided, single submitter (Variantyx Assertion Criteria 2022)	Likely Pathogenic (Sep 23, 2025)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 12207932, 36203352 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV007520029

Variantyx, Inc.

criteria provided, single submitter

(Variantyx Assertion Criteria 2022)

Likely Pathogenic
(Sep 23, 2025)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Charcot-Marie-Tooth neuropathy: clinical phenotypes of four novel mutations in the MPZ and Cx 32 genes.

Street VA, Meekins G, Lipe HP, Seltzer WK, Carter GT, Kraft GH, Bird TD.

Neuromuscul Disord. 2002 Oct;12(7-8):643-50.

PubMed [citation]

PMID:: 12207932

Disease Progression in Charcot-Marie-Tooth Disease Related to MPZ Mutations: A Longitudinal Study.

Fridman V, Sillau S, Bockhorst J, Smith K, Moroni I, Pagliano E, Pisciotta C, Piscosquito G, Laurá M, Muntoni F, Bacon C, Feely S, Grider T, Gutmann L, Shy R, Wilcox J, Herrmann DN, Li J, Ramchandren S, Sumner CJ, Lloyd TE, Day J, et al.

Ann Neurol. 2023 Mar;93(3):563-576. doi: 10.1002/ana.26518. Epub 2022 Oct 28.

PubMed [citation]

PMID:: 36203352
PMCID:: PMC9977145

Details of each submission

From Variantyx, Inc., SCV007520029.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This is a nonsynonymous variant in the MPZ gene (OMIM: 159440). Pathogenic variants in this gene have been associated with autosomal dominant Charcot-Marie-Tooth disease type 1B (CMT1B). This variant has been reported in at least 2 unrelated affected individuals (PMID: 12207932, 36203352) (PS4_Moderate) and observed to segregate with disease in at least 3 individuals from one family (PMID: 12207932 ) (PP1). This variant lies within a known hotspot for pathogenic variants or a well-established critical functional domain of the MPZ protein (PM1) and multiple computational algorithms predict a deleterious effect for this variant (REVEL score: 0.692) (PP3). This variant has a 0.0009% maximum allele frequency in non-founder control populations (https://gnomad.broadinstitute.org/) (PM2). Based on the current evidence, this variant is classified as likely pathogenic for autosomal dominant Charcot-Marie-Tooth disease type 1B (CMT1B).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 27, 2026

ClinVar

Relating variation to medicine